A G protein-coupled receptor (GPCR)is a type of cell membrane receptor that is involved in the transduction of extracellular signals across the cell membrane. GPCRs are also known as seven-transmembrane receptors because they typically have seven transmembrane domains that span the lipid bilayer of the cell membrane.
GPCRs are activated by the binding of extracellular ligands, such as hormones, neurotransmitters, and sensory stimuli. Upon ligand binding, a conformational change occurs in the receptor, which activates an intracellular signaling pathway mediated by a G protein. G proteins are a family of intracellular proteins that act as molecular switches, turning on or off specific signaling pathways in response to GPCR activation.
Activation of GPCRs can lead to a wide range of cellular responses, including changes in gene expression, enzyme activity, ion channel activity, and cellular metabolism. These cellular responses are involved in a wide range of physiological processes, including vision, taste, smell, neurotransmission, hormone signaling, and immune response.
GPCRs are a target for many drugs, with over a third of all currently available drugs targeting GPCRs. Examples of drugs that target GPCRs include antihistamines, beta-blockers, and serotonin reuptake inhibitors. Dysregulation of GPCRs has also been implicated in various diseases, including cancer, cardiovascular disease, and neurological disorders.
There are many different types of G protein-coupled receptors (GPCRs), which can be classified into several families based on their sequence homology and ligand binding properties. Here are some of the major families of GPCRs:
- Rhodopsin-like receptors: This is the largest family of GPCRs, and it includes receptors for neurotransmitters such as dopamine, serotonin, and adrenaline, as well as receptors for sensory stimuli such as light and odorants.
- Secretin-like receptors: This family includes receptors for peptide hormones such as glucagon, secretin, and parathyroid hormone.
- Metabotropic glutamate receptors: These receptors are involved in neurotransmission in the central nervous system, and they are activated by the neurotransmitter glutamate.
- Adhesion GPCRs: These receptors are involved in cell-cell interactions, and they contain large extracellular domains that are involved in cell adhesion and recognition.
- Frizzled receptors: These receptors are involved in the Wnt signaling pathway, which plays a critical role in embryonic development and tissue homeostasis.
- Taste receptors: These receptors are involved in the perception of taste, and they are activated by different types of tastants such as sweet, bitter, and umami.
- Orphan receptors: These are GPCRs whose ligands have not yet been identified, and they are the subject of ongoing research to determine their functions and potential therapeutic applications.
Each family of GPCRs has unique structural and functional features, and they are involved in a wide range of physiological processes. Understanding the functions of GPCRs and their signaling pathways is critical for developing new drugs and treatments for a wide range of diseases.
G proteins are a family of intracellular signaling proteins that play a crucial role in transducing extracellular signals across the cell membrane in response to activation of G protein-coupled receptors (GPCRs). G proteins are molecular switches that can be turned on or off by GPCRs, and they mediate a wide range of cellular responses.
When a GPCR is activated by ligand binding, it undergoes a conformational change that allows it to interact with a G protein. The G protein is a trimeric protein composed of alpha, beta, and gamma subunits. When the GPCR interacts with the G protein, the GDP molecule bound to the alpha subunit is exchanged for GTP, causing a conformational change that activates the G protein.
The activated alpha subunit can then interact with a variety of downstream effectors, including enzymes, ion channels, and second messengers, leading to changes in cellular activity. The beta and gamma subunits can also interact with downstream effectors, independent of the alpha subunit.
There are several families of G proteins, including Gs, Gi, Gq, and G12/13, which differ in their downstream effectors and cellular responses. For example, Gs proteins stimulate the activity of adenylate cyclase, leading to an increase in cyclic AMP (cAMP), while Gi proteins inhibit adenylate cyclase activity and decrease cAMP levels.
Dysregulation of G protein signaling has been implicated in various diseases, including cardiovascular disease, metabolic disorders, and cancer. Drugs that target G proteins or GPCRs are widely used in the treatment of various diseases, including hypertension, asthma, and depression.